Francisella tularensis is a highly infectious bacterium that is classified as a CDC Category A biological agent. The primary objectives of this proposal is to understand the role of gene products of a recently discovered "pathogenicity island" found in F. tularensis. The pathogenicity island was discovered by the applicants and collaborators, and found to contain genes needed for F. tularensis to grow in macrophages and cause disease in mice. An unusual feature of most of the genes of the pathogenicity island is that they were imported from a protozoa related to the causative agent of malaria. The experiments proposed in this application are designed to characterize the protein products of the pathogenicity island and to determine if some of the proteins play a role in disease that is similar to their counterparts in protozoan pathogens. Genetic and biochemical techniques will be used to characterize the expression pattern and the biochemical nature of the proteins encoded by the pathogenicity island, and microscopy approaches will be used to determine how the proteins affect macrophages infected by F. tularensis. [unreadable] [unreadable] [unreadable]